Journal of Clinical Apheresis 00:00–00 (2014)
Case Report The Use of Plasma Exchange in Hashimoto’s Encephalopathy: A Case Report and Review of the Literature Melissa K. Cook,1 Mark Malkin,2 and Matthew S. Karafin3,4* 1
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Department of Neurology, Virginia Commonwealth University, Richmond, Virginia 3 Medical Sciences Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin 4 Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
2
Hashimoto’s Encephalopathy (HE) is a very rare condition characterized by psychosis, seizures, cognitive fluctuations, and myoclonus. In a few published cases, plasma exchange has been used due to the theoretical removal of antithyroid peroxidase antibodies (anti-TPO), one of the postulated causes of the condition. We report a case of HE treated by plasma exchange where no clinical or neurophysiologic improvement was observed despite documented reduction of the anti-TPO antibody to levels below the limits of laboratory detection. We discuss these findings in the context of the known literature for this disease process. J. Clin. Apheresis 00:000–000, C 2014 Wiley Periodicals, Inc. 2014. V Key words: Hashimoto’s encephalopathy; plasma exchange; pheresis indications
INTRODUCTION
Hashimoto’s Encephalopathy (HE) is one possible cause of encephalopathy of unknown origin. With an estimated prevalence of 2/100,000 [1], it is a rare neuropsychiatric syndrome defined by encephalopathy and elevated antithyroid antibodies in the absence of nervous system infection, tumor, or stroke [2–4]. The clinical presentation is highly variable, and common clinical features include psychiatric manifestations, such as depression, mania, psychosis, and hallucinations [5–9], seizures [10,11], focal neurologic deficits, such as cognitive fluctuations, ataxia, and myoclonus [12–17], and an amnestic syndrome [18]. While steroids remain the first line treatment for this disease process [19], some case reports have documented clinical improvement with plasma exchange [10,20–26]. The current case report documents an unsuccessful trial of plasma exchange therapy in a patient with HE. We correlate the changes in anti-TPO titers with the plasma exchange therapy, and review our findings in the context of the available literature on this rare disease process. CASE REPORT
A 63-year-old African-American female initially presented to our hospital in status epilepticus. Her seizC 2014 Wiley Periodicals, Inc. V
ures were associated with a fluctuating cognitive status, paranoia, and starring spells. Medical records revealed that she had a diagnosis of seizures for the past three years from an unclear etiology, and received routine antiseizure medications (AEDs) for seizure control (Levetiracetam and Lacosamide). Other medical, family, and social history were noncontributory. On presentation, she was nonverbal, opening eyes only to pain, and not following commands. Despite pentobarbital, the patient continued to show evidence of seizure activity with stimulus-induced rhythmic, periodic, or ictal discharges, and left temporal epileptiform discharges on electroencephalogram (EEG). She consequently required 10 days of intubation and sedation while on a pentobarbital drip for seizure activity control. An extensive diagnostic workup performed during her admission was negative for evidence of acute cerebral infection, stroke, or undiagnosed neoplasm. Specifically, she was negative for a new stroke by serial *Correspondence to: Matthew S. Karafin, Blood Center of Wisconsin, 638 N 18th, Street, Milwaukee, WI 53201, USA. E-mail: [email protected]. Received 10 February 2014; Accepted 30 July 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21353
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Cook et al.
magnetic resonance imaging (MRI) scans (precontrast and postcontrast). She was afebrile during her hospital course, and her cerebrospinal fluid (CSF) and blood cultures were negative for infectious organisms (elevated protein only). Tests for human immunodeficiency virus (HIV), syphilis (VDRL), herpes simplex virus (HSV), Lyme disease, blastomyces, histoplasma, and prion disease (14:3:3) were all negative. Lastly, all markers of systemic autoimmune and paraneoplastic diseases were negative, including, antineutrophil antibodies (ANA), rheumatoid factor (RF), Sjogren’s disease markers (anti-SS-A, SS-B), angiotensin converting enzyme (marker for neurosarcoidosis), carcinoembryonic antigen (CEA), cancer antigen (CA), anticyclic citrullinated peptide (anti-CCP IgG/IgA), antiglutamic acid decarboxylase (anti-GAD), anti-N-methyl-D-aspartate receptor (anti-NMDAR), intact parathyroid hormone (iPTH) and Tau. A chest CT incidentally showed a thyroid nodule that was determined to be papillary thyroid carcinoma (stage III T3N0MX). She was started on levothyroxine and found to be positive for anti-TPO. Of note, her initial titer was found to be markedly elevated (699 IU/ml). Because of the presence of encephalopathy and elevated antithyroid antibodies without evidence of infection, tumor, or stroke, a working diagnosis of HE was made. An initial steroid trial (250 mg IV q 6 h for three days) elicited minimal changes in her physical exam and EEG. However, subsequent intravenous immune globulin (IVIG) (2 g/kg over five days) treatment was associated with a modest improvement in a previously restricted area of diffusion on the right frontal sulcus by magnetic resonance imaging (MRI). With treatment, she became more verbal, responded to commands, and her paranoia improved. She was subsequently discharged 10 weeks after admission to a rehabilitation facility on levothyroxine and oral prednisone in stable condition. Two months later, she was readmitted for worsening paranoia and aggressive behavior. On admission, it was noted that she was refusing her steroid and thyroid medications and had not taken these medications for a number of days. A repeat anti-TPO titer was 96 IU/ml. Repeat EEG showed intermittent delta wave changes similar to her initial presentation, and was concerning for seizure activity. Repeat imaging and laboratory work-up was again negative on all measures. Because of her limited previous response to steroids, a trial of plasma exchange was requested. She received five, one plasma volume, plasma exchange treatments using 80% 5%-albumin and 20% normal saline every other day (including weekends). No acute adverse events were noted during any procedure, and her anti-TPO titers fell to levels below the limits of detection by the 5th treatment (from 96 IU/ml initial, 76 IU/ml after first, 33 IU/ml after second, 29 IU/ml after third, 22 Journal of Clinical Apheresis DOI 10.1002/jca
IU/ml after fourth and
Case Report The Use of Plasma Exchange in Hashimoto’s Encephalopathy: A Case Report and Review of the Literature Melissa K. Cook,1 Mark Malkin,2 and Matthew S. Karafin3,4* 1
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Department of Neurology, Virginia Commonwealth University, Richmond, Virginia 3 Medical Sciences Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin 4 Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
2
Hashimoto’s Encephalopathy (HE) is a very rare condition characterized by psychosis, seizures, cognitive fluctuations, and myoclonus. In a few published cases, plasma exchange has been used due to the theoretical removal of antithyroid peroxidase antibodies (anti-TPO), one of the postulated causes of the condition. We report a case of HE treated by plasma exchange where no clinical or neurophysiologic improvement was observed despite documented reduction of the anti-TPO antibody to levels below the limits of laboratory detection. We discuss these findings in the context of the known literature for this disease process. J. Clin. Apheresis 00:000–000, C 2014 Wiley Periodicals, Inc. 2014. V Key words: Hashimoto’s encephalopathy; plasma exchange; pheresis indications
INTRODUCTION
Hashimoto’s Encephalopathy (HE) is one possible cause of encephalopathy of unknown origin. With an estimated prevalence of 2/100,000 [1], it is a rare neuropsychiatric syndrome defined by encephalopathy and elevated antithyroid antibodies in the absence of nervous system infection, tumor, or stroke [2–4]. The clinical presentation is highly variable, and common clinical features include psychiatric manifestations, such as depression, mania, psychosis, and hallucinations [5–9], seizures [10,11], focal neurologic deficits, such as cognitive fluctuations, ataxia, and myoclonus [12–17], and an amnestic syndrome [18]. While steroids remain the first line treatment for this disease process [19], some case reports have documented clinical improvement with plasma exchange [10,20–26]. The current case report documents an unsuccessful trial of plasma exchange therapy in a patient with HE. We correlate the changes in anti-TPO titers with the plasma exchange therapy, and review our findings in the context of the available literature on this rare disease process. CASE REPORT
A 63-year-old African-American female initially presented to our hospital in status epilepticus. Her seizC 2014 Wiley Periodicals, Inc. V
ures were associated with a fluctuating cognitive status, paranoia, and starring spells. Medical records revealed that she had a diagnosis of seizures for the past three years from an unclear etiology, and received routine antiseizure medications (AEDs) for seizure control (Levetiracetam and Lacosamide). Other medical, family, and social history were noncontributory. On presentation, she was nonverbal, opening eyes only to pain, and not following commands. Despite pentobarbital, the patient continued to show evidence of seizure activity with stimulus-induced rhythmic, periodic, or ictal discharges, and left temporal epileptiform discharges on electroencephalogram (EEG). She consequently required 10 days of intubation and sedation while on a pentobarbital drip for seizure activity control. An extensive diagnostic workup performed during her admission was negative for evidence of acute cerebral infection, stroke, or undiagnosed neoplasm. Specifically, she was negative for a new stroke by serial *Correspondence to: Matthew S. Karafin, Blood Center of Wisconsin, 638 N 18th, Street, Milwaukee, WI 53201, USA. E-mail: [email protected]. Received 10 February 2014; Accepted 30 July 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21353
2
Cook et al.
magnetic resonance imaging (MRI) scans (precontrast and postcontrast). She was afebrile during her hospital course, and her cerebrospinal fluid (CSF) and blood cultures were negative for infectious organisms (elevated protein only). Tests for human immunodeficiency virus (HIV), syphilis (VDRL), herpes simplex virus (HSV), Lyme disease, blastomyces, histoplasma, and prion disease (14:3:3) were all negative. Lastly, all markers of systemic autoimmune and paraneoplastic diseases were negative, including, antineutrophil antibodies (ANA), rheumatoid factor (RF), Sjogren’s disease markers (anti-SS-A, SS-B), angiotensin converting enzyme (marker for neurosarcoidosis), carcinoembryonic antigen (CEA), cancer antigen (CA), anticyclic citrullinated peptide (anti-CCP IgG/IgA), antiglutamic acid decarboxylase (anti-GAD), anti-N-methyl-D-aspartate receptor (anti-NMDAR), intact parathyroid hormone (iPTH) and Tau. A chest CT incidentally showed a thyroid nodule that was determined to be papillary thyroid carcinoma (stage III T3N0MX). She was started on levothyroxine and found to be positive for anti-TPO. Of note, her initial titer was found to be markedly elevated (699 IU/ml). Because of the presence of encephalopathy and elevated antithyroid antibodies without evidence of infection, tumor, or stroke, a working diagnosis of HE was made. An initial steroid trial (250 mg IV q 6 h for three days) elicited minimal changes in her physical exam and EEG. However, subsequent intravenous immune globulin (IVIG) (2 g/kg over five days) treatment was associated with a modest improvement in a previously restricted area of diffusion on the right frontal sulcus by magnetic resonance imaging (MRI). With treatment, she became more verbal, responded to commands, and her paranoia improved. She was subsequently discharged 10 weeks after admission to a rehabilitation facility on levothyroxine and oral prednisone in stable condition. Two months later, she was readmitted for worsening paranoia and aggressive behavior. On admission, it was noted that she was refusing her steroid and thyroid medications and had not taken these medications for a number of days. A repeat anti-TPO titer was 96 IU/ml. Repeat EEG showed intermittent delta wave changes similar to her initial presentation, and was concerning for seizure activity. Repeat imaging and laboratory work-up was again negative on all measures. Because of her limited previous response to steroids, a trial of plasma exchange was requested. She received five, one plasma volume, plasma exchange treatments using 80% 5%-albumin and 20% normal saline every other day (including weekends). No acute adverse events were noted during any procedure, and her anti-TPO titers fell to levels below the limits of detection by the 5th treatment (from 96 IU/ml initial, 76 IU/ml after first, 33 IU/ml after second, 29 IU/ml after third, 22 Journal of Clinical Apheresis DOI 10.1002/jca
IU/ml after fourth and
